Agresti Nicholas, Lalezari Jacob P, Amodeo Phillip P, Mody Kabir, Mosher Steven F, Seethamraju Harish, Kelly Scott A, Pourhassan Nader Z, Sudduth C David, Bovinet Christopher, ElSharkawi Ahmed E, Patterson Bruce K, Stephen Reejis, Sacha Jonah B, Wu Helen L, Gross Seth A, Dhody Kush
Southeast Georgia Health System, 2415 Parkwood Drive, Brunswick, GA, 31520, USA.
CytoDyn, 1111 Main Street, Suite 660 Vancouver, WA, 98660, USA.
J Transl Autoimmun. 2021;4:100083. doi: 10.1016/j.jtauto.2021.100083. Epub 2021 Jan 6.
Coronavirus disease 2019 (COVID-19) is associated with considerable morbidity and mortality. The number of confirmed cases of infection with SARS-CoV-2, the virus causing COVID-19 continues to escalate with over 70 million confirmed cases and over 1.6 million confirmed deaths. Severe-to-critical COVID-19 is associated with a dysregulated host immune response to the virus, which is thought to lead to pathogenic immune dysregulation and end-organ damage. Presently few effective treatment options are available to treat COVID-19. Leronlimab is a humanized IgG4, kappa monoclonal antibody that blocks C-C chemokine receptor type 5 (CCR5). It has been shown that in patients with severe COVID-19 treatment with leronlimab reduces elevated plasma IL-6 and chemokine ligand 5 (CCL5), and normalized CD4/CD8 ratios. We administered leronlimab to 4 critically ill COVID-19 patients in intensive care. All 4 of these patients improved clinically as measured by vasopressor support, and discontinuation of hemodialysis and mechanical ventilation. Following administration of leronlimab there was a statistically significant decrease in IL-6 observed in patient A (p=0.034) from day 0-7 and patient D (p=0.027) from day 0-14. This corresponds to restoration of the immune function as measured by CD4+/CD8+ T cell ratio. Although two of the patients went on to survive the other two subsequently died of surgical complications after an initial recovery from SARS-CoV-2 infection.
2019冠状病毒病（COVID-19）与相当高的发病率和死亡率相关。导致COVID-19的病毒——严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的确诊感染病例数持续攀升，确诊病例超过7000万例，确诊死亡病例超过160万例。重症至危重症COVID-19与宿主对该病毒的免疫反应失调有关，这被认为会导致致病性免疫失调和终末器官损伤。目前，治疗COVID-19的有效治疗选择很少。leronlimab是一种人源化IgG4κ单克隆抗体，可阻断C-C趋化因子受体5（CCR5）。研究表明，在重症COVID-19患者中，使用leronlimab治疗可降低血浆中升高的白细胞介素-6（IL-6）和趋化因子配体5（CCL5），并使CD4/CD8比值恢复正常。我们对4名重症监护病房的危重症COVID-19患者使用了leronlimab。通过血管升压药支持、停止血液透析和机械通气来衡量，所有这4名患者的临床症状均有改善。在使用leronlimab后，患者A在第0至7天（p=0.034）和患者D在第0至14天（p=0.027）观察到IL-6有统计学意义的下降。这对应于通过CD4+/CD8+T细胞比值衡量的免疫功能的恢复。尽管其中两名患者最终存活，但另外两名患者在从SARS-CoV-2感染中初步恢复后，随后死于手术并发症。
